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Identifying New Combination Drug Classes for Hypertension and Diabetes
A review of Molecular characterization of new selective peroxisome proliferator–activated receptor gamma modulators with angiotensin receptor blocking activity.
Note: This is a review of the published article listed below. All information, quotes, figures, methods, and findings mentioned in this review are from that article, and are the property of its authors and/or the publication in which the article originally appeared.
Schupp and colleagues (2005) analyzed the functional activity of two angiotensin receptor blockers (ARBs), telmisartan and irbesartan, as new selective peroxisome proliferator-activated receptor (PPAR) modulators (SPPARMs). Agilent’s mouse oligo microarrays were used to determine the effect of both ARBs and pioglitazone (a PPAR activator) on gene expression in mouse 3T3-L1 preadipocytes. This study identifies and confirms that these two ARBs do indeed function as SPPARMs, and potentially provide exciting new therapeutic options for more effective cardiovascular risk management in metabolic diseases. These novel SSPARMs may allow development of new pharmacological drug classes that combine potent antihypertensive and antidiabetic actions, without the adverse effects associate with the glitazone family.
Figure 1. Divergent effects of ARBs and pioglitazone on gene expression.
A: Treated adipocyte samples were subjected to four rounds of hybridization to Agilent microarrays, and functionally relevant PPAR and fat-cell physiology genes were clustered and divided into similarly and differentially regulated genes. B: Randomly selected differentially-expressed genes were confirmed by real-time PCR. *P < 0.05 vs. vehicle-treated cells. Most genes with identified PPREs in their promoters were similarly regulated by both pioglitazone and the ARBs. Consistent with selective cofactor recruitment and binding by the ARBs, they produced distinctive gene expression profiles, identifying them as selective PPAR ligands. There were also distinct differences in the regulation of genes between the two ARBs, suggesting distinguishing mechanisms.
Title: Molecular characterization of new selective peroxisome proliferator–activated receptor gamma modulators with angiotensin receptor blocking activity
Authors: H, Janke J, Helleboid S, Hennuyer N, Ruiz P, Unger T, Staels B, and Kintscher U.
Journal: Diabetes. 2005 Dec;54(12):3442-52.
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